It came as Syrian opposition campaigners claimed Syrian forces had fired chemical weapons from multiple rocket launchers at rebels surrounding an army base in the town of Adra on the north-eastern outskirts of Damascus, killing two fighters and wounding 23.

"Doctors are describing the chemical weapon used as phosphorus that hits the nervous system and causes imbalance and loss of consciousness," said Mohammad al-Doumani, an activist in the nearby town of Douma, where the wounded were transported.

"The two fighters were very close to where the rockets exploded and they died swiftly."

The authorities and rebels accused each other of firing a missile carrying chemicals there.

Elsewhere, Israel launched a missile strike which destroyed a Syrian army outpost in the Golan Heights, in one of the most serious security incidents between the two countries since Syria's civil war began.

Israel says it holds the Syrian regime responsible for gunfire from Syria that hit two Israeli patrols in the last 24 hours.

Spanner in the summit

Mr Alkhatib was picked to head the Western and Gulf-backed National Coalition for Syrian Revolutionary and Opposition Forces, which was formed in Qatar in November.

He was seen as a moderate bulwark against the rising influence of Al Qaeda linked jihadist forces.

He quit after the coalition berated him for offering Mr Assad a deal and after the group went ahead, despite his objections, with steps to form a provisional government that would have further diminished his authority.

"I had promised the great Syrian people and promised God that I would resign if matters reached some red lines," Mr Alkhatib said in a statement on his official Facebook page, without explaining exactly what had prompted his resignation.

"Now I am fulfilling my promise and announcing my resignation from the National Coalition in order to be able to work with freedom that cannot be available within the official institutions."

Syrian opposition leaders are due to attend an Arab League summit this week, Qatar said earlier on Sunday, looking for more support for their armed uprising.

Michael Stephens, researcher at the Royal United Services Institute in Doha, said Mr Alkhatib's resignation throws a spanner into the summit.

"The premise of the summit is to determine whether the opposition has a legitimate right to sit with Arab states," Mr Stephens said.

"While Khatib may have blamed the EU summit, it is well known that the Arab League is meeting today, and his resignation will have a serious effect on the process."

Asked to comment on Mr Alkhatib's resignation, Qatari foreign minister Sheikh Hamad bin Jassim al-Thani said in Doha: "We are very sorry for this, and I hope he reviews his resignation."

US secretary of state John Kerry, on a trip to Baghdad, expressed regret at Mr Alhatib's decision.

"With respect to Moaz Alkhatib, I am personally sorry to see him go because I like him on a personal level and because I have appreciated his leadership, but the notion that he might resign has frankly been expressed by him on many different occasions in many different places and it is not a surprise," Mr Kerry said.

He made an unannounced visit to Iraq on Sunday and said he told prime minister Nuri al-Maliki of his concern about Iranian flights over Iraq carrying arms to Syria.

"Anything that supports president Assad is problematic," Mr Kerry said.